African Americans are at increased risk for tobacco related morbidity and mortality despite smoking fewer cigarettes per day than the general population. Within this competing continuation, our experienced, multidisciplinary team proposes to conduct collaborative research building upon a strong foundation of smoking cessation intervention studies among urban African American smokers. Our previous research demonstrated efficacy of bupropion for smoking cessation among moderate to heavy smokers, efficacy of health education counseling and limitations in nicotine gum use among light smokers. We plan to extend these efforts to further evaluate smoking behavior and biobehavioral interventions and to explore factors associated with drug activity and behavior change with the goal of enhancing abstinence outcomes. Our specific objectives are to 1) evaluate the efficacy of sustained release bupropion in combination with health education (HE) counseling for smoking cessation among urban African American light smokers, 2) characterize CYP2A6 activity by evaluating phenotype (3HC/cotinine ratio ) and CYP2A6 genotype, 3) characterize CYP2B6 activity by evaluating phenotype and CYP2B6 genotype to assess nicotine and bupropion metabolite levels, 4) explore associations of these phenotypic and genotypic variables with smoking cessation and response to bupropion. This randomized, placebo-controlled study will be conducted at a community-based clinic, Swope Parkway Health Center in Kansas City, Missouri. The primary outcome is 7-day point prevalence smoking abstinence at 6 months confirmed with salivary cotinine. Five hundred forty (270 in each arm) African American light smokers will be randomly assigned to an active bupropion and health education (HE) counseling (Tx) condition or to a placebo and HE comparison (C) condition. Bupropion treatment (active or placebo) will last for 7 weeks (one week prior to quit date, six weeks post quit date). All participants will be offered six HE sessions. The proposed research provides a unique opportunity to evaluate psychosocial and biological mechanisms related to drug use and treatment outcomes. Identifying individuals for whom treatments are most effective and, in contrast, identifying characteristics related to relapse risk will be critical to advancing tailored tobacco use treatment and health promotion for African American smokers.